Hypoxia and aging

Eukaryotic cells require sufficient oxygen (O2) for biological activity and survival. When the oxygen demand exceeds its supply, the oxygen levels in local tissues or the whole body decrease (termed hypoxia), leading to a metabolic crisis, threatening physiological functions and viability. Therefore, eukaryotes have developed an efficient and rapid oxygen sensing system: hypoxia-inducible factors (HIFs). The hypoxic responses are controlled by HIFs, which induce the expression of several adaptive genes to increase the oxygen supply and support anaerobic ATP generation in eukaryotic cells. Hypoxia also contributes to a functional decline during the aging process. In this review, we focus on the molecular mechanisms regulating HIF-1α and aging-associated signaling proteins, such as sirtuins, AMP-activated protein kinase, mechanistic target of mTOR(definition)-inhibiting drug studied for extending healthspan and lifespan." style="text-decoration:underline dotted; text-underline-offset:2px; cursor:help;">rapamycin(definition) complex 1, UNC-51-like kinase 1, and nuclear factor κB, and their roles in aging and aging-related diseases. In addition, the effects of prenatal hypoxia and obstructive sleep apnea (OSA)-induced intermittent hypoxia have been reviewed due to their involvement in the progression and severity of many diseases, including cancer and other aging-related diseases. The pathophysiological consequences and clinical manifestations of prenatal hypoxia and OSA-induced chronic intermittent hypoxia are discussed in detail. Deficient oxygen supplies to the body’s tissues and a reduced ability to deal with the cellular stress of low oxygen availability both contribute to the ageing process. Eui-Ju Yeo from Gachon University in Incheon, South Korea, reviews the links between insufficient oxygen, a condition known as hypoxia, and the functional decline associated with getting old. Yeo highlights the role that the oxygen-sensing proteins known as hypoxia-inducible factors (HIFs) play in facilitating oxygen supply and regulating energy production under limited oxygen conditions. HIFs also interact with a series of signaling proteins that, when abnormally activated, contribute to many aging-associated diseases. Yeo singles out two hypoxia-related health problems, prenatal hypoxia during early brain development and obstructive sleep apnea, and discusses how they can accelerate aging in various ways.